Red Blood Cell Omega-3 Fatty Acid Composition and Psychotropic Drug Use in Older Adults: Results from the MAPT Study.

Low docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration has been associated with the development of some psychiatric disorders. OBJECTIVES: to assess the association between red blood cell (RBC) DHA-EPA concentration and psychotropic drug use in older adults and between the 1-year change in RBC DHA-EPA and psychotropic drug use at 12 months. DESIGN: secondary analysis of multicenter, randomized controlled trial testing multidomain intervention and/or n-3 PUFA supplement on cognitive function (MAPT study). SETTING: France, 2008-2014. PARTICIPANTS: 1680 participants ≥70 years, community-dwelling were included. MEASUREMENTS: Psychotropic drug use was self-reported during medical interviews and assessments. RBC n-3 PUFA concentration was defined by % of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) among total fatty acids. Logistic regressions models controlling for age, sex, education, depression risk and intervention group were used. RESULTS: 1594 participants had baseline DHA-EPA concentration available (mean age=75.5±4.5 years, 65% females). At baseline, participants with DHA-EPA ≤4.82% (lowest quartile) reported higher prevalence of use of overall psychotropic drugs (34.0% vs 24.4%; aOR=1.33, 95%CI=[1.03-1.72]), anxiolytic/hypnotic drugs (25.0% vs 18.2%; aOR=1.42, 95%CI=[1.07-1.89]), and antidepressants (18.3% vs 13.5%; aOR=1.25, 95%CI=[0.93-1.72]) than participants with higher DHA-EPA. Participants who experienced an increase in DHA-EPA from baseline were less likely to use a psychotropic drug at 12 months than participants with no change or a decrease (aOR=0.72, 95%CI=[0.55-0.96]). CONCLUSION: Low RBC DHA-EPA concentration was independently associated with psychotropic drug use. Future studies are needed to assess whether low RBC DHA-EPA is a risk marker for psychotropic drug use in older adults and to better understand underlying pathophysiological mechanisms. Registration number: ClinicalTrials.gov database (NCT00672685).

Self-rated health and risk of incident dementia: a community-based elderly cohort, the 3C study.

OBJECTIVES: We examined the relationship between self-rated health and incident dementia, and investigated the impact of cognitive complaints, depressive symptoms, and functional status on this relationship. METHODS: Participants of the 3C Study, a prospective cohort study composed of 8,169 community-dwelling persons aged ≥65 years, were asked to rate their health at the baseline examination in 1999-2001. They were followed for a median of 6.7 years during which dementia was screened and diagnosed. Hazard ratios (HR) of dementia according to baseline self-rated health (good, fair, or poor) were estimated with a Cox model adjusted for potential confounders. RESULTS: During the 46,990 person-years of follow-up, 618 participants developed dementia. Risk of dementia was increased in participants with poor (adjusted HR 1.70, 95% confidence interval [CI] 1.22-2.37) or fair (adjusted HR 1.34, 95% CI 1.13-1.59) self-rated health compared to those with good self-rated health. Poor self-rated health was associated with both AD (1.48, 1.00-2.24) and vascular dementia (3.38, 1.25-9.17). Self-rated health was a stronger predictor of dementia in participants without cognitive complaints (risk of dementia in subjects without cognitive complaints rating their health as poor: 1.96 [1.24-3.09], p = 0.004) and in those without functional disability. CONCLUSIONS: Participants rating their health as poor or fair at baseline were at increased risk of incident dementia during follow-up. Self-rated health could help raise awareness of medical doctors about a patient's risk of dementia, especially in those without conditions indicative of potential cognitive impairment.

High levels of women's satisfaction and compliance with transdermal contraception: results from a European multinational, 6-month study.

OBJECTIVE: To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch. METHODS: Women (18-46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 µg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods. RESULTS: Of the 778 participants, 36.8% (n = 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n = 334) and barrier methods (21.5%, n = 106). Of oral contraception users, 63.5% (n = 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8% (n = 260) reporting missed doses. After 3 and 6 cycles, >80% of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated. CONCLUSION: Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential to offer high compliance and efficacy.

Characteristics of hormone therapy, cognitive function, and dementia: the prospective 3C Study.

OBJECTIVES: To examine the association between hormone therapy (HT) and cognitive performance or dementia, focusing on the duration and type of treatment used, as well as the timing of initiation of HT in relation to the menopause. METHODS: Women 65 years and older were recruited in France as part of the Three City Study. At baseline and 2- and 4-year follow-up, women were administered a short cognitive test battery and a clinical diagnosis of dementia was made. Detailed information was also gathered relating to current and past HT use. Analysis was adjusted for a number of sociodemographic, behavioral, physical, and mental health variables, as well as APOE epsilon4. RESULTS: Among 3,130 naturally postmenopausal women, current HT users performed significantly better than never users on verbal fluency, working memory, and psychomotor speed. These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial. However, initiation of HT close to the menopause was not associated with better cognition. HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with APOE epsilon4. CONCLUSIONS: Current hormone therapy (HT) was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used. We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life. Current HT may decrease the risk of dementia associated with the APOE epsilon4 allele.

[Isolated autobiographical amnesia: a neurological basis?]. / Amnésie autobiographique isolée : une origine neurologique ?

INTRODUCTION: The term "autobiographical memory" (AuM) refers to contextually bound experiences that occurred in a specific time, place, and affective setting. AuM is a component of memory commonly impaired in amnestic disorders. Alteration occurs rarely in isolation but rather in the setting of a larger memory impairment. Isolated AuM deficit is a controversial clinical entity, however, recently reported in the context of temporal lobe epilepsy. This study aims at characterizing this poorly documented clinical syndrome and at discussing its potential pathophysiological basis. PATIENTS AND METHODS: We studied a group of three subjects with a history of pharmacosensitive epilepsy and severe AuM complaints. They all were submitted to a neuropsychological evaluation that included an extensive episodic memory assessment, along with wake/sleep electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). RESULTS: We observed the following findings: preserved autonomy and intact global cognitive functioning; normal performance to standardized episodic memory assessment, contrasting with decreased performance to specific AuM evaluation; frontal and/or temporal epileptic activity on EEG; and normal structural brain MRI. CONCLUSION: We reported on a group of patients exhibiting selective impairment of some components of personal memory, associated with interictal frontal and/or temporal abnormalities on EEG. To account for these findings, we hypothesise that interictal epileptic-related activity is impeding long-term consolidation or storage of autobiographical material.

[Pure progressive amnesia: an amnestic syndrome with preserved independence in daily life]. / L'amnésie pure progressive : un syndrome amnésique avec préservation de l'autonomie.

INTRODUCTION: Pure progressive amnesia, a form of progressive focal cortical atrophy is thought to represent the early stages of a rare form of Alzheimer's disease (AD). This syndrome is characterized by the insidious and slowly progressive breakdown of memory, in the absence of a significant impairment in other cognitive domains or in the realm of behavior. The aims of the present study were to contribute to the characterization of this poorly documented type of amnesia, to compare it with other forms of amnestic syndromes resulting from lesions to the medial temporal lobes and to discuss its potential pathophysiological basis. PATIENTS AND METHOD: We carried out three single case studies in patients presenting with pure progressive amnesia. They all underwent a neuropsychological evaluation that included an extensive assessment of spatial and recognition memory, along with brain magnetic resonance imaging and a cerebral blood flow study. RESULTS: All three patients had a severe deficit in the storage of context-free information, along with a severe visual recognition memory impairment, as previously reported in a case study on a patient with pure progressive amnesia (Cognitive Neuropsychology 23 (2006) 1230-1247). Yet, spatial memory remained well preserved, and patients maintained totally independent in everyday life. In addition, a significant atrophy of the medial temporal structures was found. DISCUSSION: This specific pattern of impairment differs from other types of amnestic syndromes after medial temporal damage and raises the question of lesional topography, as well as possible compensatory phenomena. We suggest that pure progressive amnesia results from selective damage to the ventral subhippocampal route into the hippocampal formation leading to impaired context-free memory. Spatial memory may remain intact because the dorsal parahippocampal route into the hippocampus remains functional. Pure progressive amnesia may contribute to a better understanding of the neural systems involved in declarative memory and provide a better understanding into the nature of the memory impairment that characterizes the initial stages of AD.

Rapid cognitive decline in Alzheimer's disease. Consensus paper.

The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different "a priori" definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

Risk profiles for mild cognitive impairment and progression to dementia are gender specific.

OBJECTIVE: To examine risk factors for mild cognitive impairment (MCI) and progression to dementia in a prospective community-based study of subjects aged 65 years and over. METHODS: 6892 participants who were over 65 and without dementia were recruited from a population-based cohort in three French cities. Cognitive performance, clinical diagnosis of dementia, and clinical and environmental risk factors were evaluated at baseline and 2-year and 4-year follow-ups. RESULTS: 42% of the population were classified as having MCI at baseline. After adjustment for confounding with logistic regression models, men and women classified as having MCI were more likely to have depressive symptomatology and to be taking anticholinergic drugs. Men were also more likely to have a higher body mass index, diabetes and stroke, whereas women were more likely to have poor subjective health, to be disabled, to be socially isolated, and to suffer from insomnia. The principal adjusted risk factors for men for progression from MCI to dementia in descending order were ApoE4 allele (OR = 3.2, 95% CI 1.7 to 5.7), stroke (OR = 2.8, 95% CI 1.2 to 6.9), low level of education (OR = 2.3, 95% CI 1.3 to 4.1), loss of Instrumental Activities of Daily Living (IADL) (OR = 2.2, 95% CI 1.1 to 4.5) and age (OR = 1.2, 95% CI 1.1 to 1.2). In women, progression is best predicted by IADL loss (OR = 3.5, 95% CI 2.1 to 5.9), ApoE4 allele (OR = 2.3, 95% CI 1.4 to 4.0), low level of education (OR = 2.2, 95% CI 1.3 to 3.6), subclinical depression (OR = 2.0, 95% CI 1.1 to 3.6), use of anticholinergic drugs (OR = 1.8, 95% CI 1.0 to 3.0) and age (OR = 1.1, 95% CI 1.1 to 1.2). CONCLUSIONS: Men and women have different risk profiles for both MCI and progression to dementia. Intervention programmes should focus principally on risk of stroke in men and depressive symptomatology and use of anticholinergic medication in women.

Undifferentiation of somatic responses to emotions in a case of functional amnesia.

The term functional amnesia (FA) has been proposed for cases of memory impairment presenting with severe retrograde amnesia in the absence of cerebral injury or history of psychiatric disturbance. Emotional flattening has often been reported alongside FA, however the mechanism of such a modification is unknown. This study aimed to explore the emotional processing in a rare case of a patient with FA complaining of severe emotional flattening. We presented ecological dynamic video stimuli conveying strong peaceful and fearful emotions to the patient and 13 controls. We then explored their emotional responses considering both conscious emotional judgements and automatic psychophysiological responses (skin conductance) and facial muscular activity (corrugator supercilii). Both patient P.P. and controls perfectly recognized the emotions conveyed by the films. However, P.P. failed to show an increased skin conductance and corrugator activity as found in controls during fearful film extracts compared with peaceful extracts. Taken together, these finding demonstrate the presence of an emotional deficit, characterized by a failure to generate appropriate somatic responses to positive and negative stimuli. Although this altered somatic processing did not interfere with PP's explicit recognition of emotion, it modified his emotional experience, thereby constituting a possible explanation for his emotional flattening. This study therefore suggests that FA is not limited to a mnemonic impairment, but is a more complex disorder, involving also the processing of emotionally loaded experiences.

Profile of memory impairment and gray matter loss in amnestic mild cognitive impairment.

The present study assessed the patterns of cortical gray matter (GM) loss in patients with amnestic mild cognitive impairment (aMCI) with distinct profiles of memory impairment, i.e. aMCI patients failing on both recall and recognition memory vs. aMCI patients showing impaired recall but preserved recognition memory. This distinction is usually not taken into account in studies on aMCI and the aim of the present study was to assess whether this distinction is useful. Twenty-eight aMCI patients and 28 matched controls subjects were included. All aMCI patients failed a recall memory task (inclusion criteria). All underwent a visual recognition memory task (DMS48). However, 12 succeeded on this task while 16 failed. Relative gray matter (GM) loss was measured using voxel-based morphometry. When comparing aMCI patients to controls regardless of the profile of memory impairment, GM loss was found in temporal, parietal and frontal areas. However, in aMCI patients with preserved recognition (but impaired recall), GM loss was confined to frontal areas. This contrasted with GM loss in the right medial temporal lobe and bilateral temporo-parietal regions in aMCI patients with impaired recall and recognition memory, a pattern of GM loss usually described in early AD. We conclude that different profiles of memory impairment in aMCI patients are associated with distinct patterns of GM loss.

Identification of subgroups in amnestic mild cognitive impairment.

The DMS48 is a visual recognition memory test designed to detect memory changes in early Alzheimer disease (AD). Patients with amnestic mild cognitive impairment (aMCI) who succeeded on this task exhibited frontal hypoperfusion on SPECT. In contrast, failure was associated with temporomesial and temporoparietal hypoperfusion, a pattern usually described in the early stages of AD. It may possible to detect patients at high risk for AD within a population of aMCI.

Clobetasol propionate shampoo 0.05% and calcipotriol solution 0.005%: a randomized comparison of efficacy and safety in subjects with scalp psoriasis.

BACKGROUND: Scalp involvement in psoriatic patients represents a common issue. Treatment of the hairy skin requires adequate pharmaceutical formulations; hence, a new specific shampoo formulation of clobetasol propionate 0.05% was developed by Galderma R&D, Inc. METHODS: For this multicenter, randomized, investigator-masked, parallel group study, 151 subjects with moderate to severe scalp psoriasis were randomized to 4 weeks of treatment with clobetasol propionate shampoo or calcipotriol solution. RESULTS: Clobetasol propionate demonstrated significantly superior efficacy to calcipotriol solution (total severity score: mean difference 0.51, 95% CI 0.05-0.97, p = 0.028; global severity score: mean difference 0.43, 95% CI 0.08-0.78, p = 0.016). Adverse events were more common in the calcipotriol group than in the clobetasol propionate shampoo group. Telangiectasia and skin atrophy did not differ significantly between treatments; however, a burning sensation was significantly more common in the calcipotriol solution group. CONCLUSIONS: Short contact therapy of scalp psoriasis with this new shampoo formulation of clobetasol propionate was significantly more effective and better tolerated than calcipotriol solution for the treatment of scalp psoriasis.

Progressive prosopagnosia: clinical and neuroimaging results.

The authors report the longitudinal case study of a patient with the right temporal variant of frontotemporal lobar degeneration. His deficit, initially limited to visuoperceptual disturbances, progressed 2 years later to a severe semantic breakdown. Neuroimaging data indicate that the underlying degenerative process, initially confined to unimodal visual associative cortices, progressed along the ventral pathways to multimodal areas in charge of integrating knowledge from various modalities (the anterior temporal lobes).

[The human perirhinal cortex]. / Le cortex périrhinal chez l'homme.

The perirhinal cortex is a structure that lies within the medial temporal lobe. In the present paper, we review current knowledge of the anatomical boundaries and functional correlates of this structure. In the past decade, numerous animal studies have attempted to understand the contribution of the perirhinal cortex to memory. Taken together, they suggest that the perirhinal cortex is crucially involved in recognition memory. This function appears to be independent from those assumed to be subserved by the hippocampus. In humans, data are scarce but tend to corroborate results found in the animal literature. The perirhinal cortex appears to support context-free (non-episodic) knowledge, such as general knowledge about the world and "item-specific" memories. Models of declarative memory that take into account the specific contribution of the perirhinal cortex are discussed, along with their potential application to early cortical neurodegenerative disorders.

Evaluation of visual recognition memory in MCI patients.

BACKGROUND: Neurofibrillary tangles seen early in Alzheimer disease (AD) initially appear in a subregion of the perirhinal cortex. In the monkey, damage to the perirhinal cortex impairs performance on visual recognition memory tasks. The authors evaluated impairment of visual recognition memory as a potential early diagnostic marker of AD. METHODS: The authors developed a visual delayed matching-to-sample task (DMS48) designed to assess visual recognition memory in humans. Twenty-three patients fulfilling the criteria of amnestic mild cognitive impairment (MCI) (mean Mini-Mental State Examination [MMSE]: 26.6, SD = 1.6) were recruited. All underwent a full neuropsychological evaluation, which included the Free and Cued Selective Reminding (FCSR) test. Their performance was compared with that of 10 patients with mild AD, 20 patients with moderate AD, 20 patients with Parkinson disease (PD), and 40 age-matched controls. RESULTS: Control subjects and patients with PD performed close to ceiling. Patients with mild AD had very low scores, while patients with moderate AD answered at random. MCI patients obtained scores that were between those of control subjects and patients with mild AD (78%, SD = 16%). MCI patients who failed on the DMS48 had lower scores on free recall (p < 0.05) and received less benefit from cueing (p < 0.01) on the FCSR than the other MCI, suggesting a profile of genuine memory impairment related to medial temporal lobe lesions. CONCLUSION: The DMS48, a test of visual recognition memory, is impaired early in the course of patients with MCI. Further studies are necessary to determine whether the evaluation of visual recognition memory may contribute to the identification of patients with AD.

[Mortality among active workers at EDG-GDF: social and occupational disparities and evolution]. / La mortalité des salariés d'EDF-GDF: disparités socioprofessionnelles et évolution.

BACKGROUND: Two studies, conducted in the eighties and the nineties, reported that mortality was lower in the French national electric and gas company (EDF-GDF) the utility workers than in the general French population. The purpose of our study was to compare the mortality of these 140,000 utility workers to that of the French population of the same age for the period from 1997 to 2001. Secondly we aimed to assess the disparities of mortality among the workforce according to demographic and socioprofessional criteria. Finally, we analyzed the evolution of this mortality over the last twenty years. METHODS: We undertook a cross-sectional study using the indirect standardization method. RESULTS: Risk of death was lower in the utility workers than in the French population (SMR=54% for men, and 58% for women). These differences had increased over the last twenty years for each main cause of death (cancers, cardio-vascular diseases and accidents). The reported excess of brain cancer death risk raises etiologic questions. Moreover, we noticed important social disparities in the workforce, increasing with time. CONCLUSION: The well-known "healthy worker effect" seems to be particularly important in the EDF-GDF company. The workers have a high level of living conditions and good working conditions, although internal social disparities persist. Further studies in other large corporations are greatly needed for comparisons.

The Snodgrass and Vanderwart set revisited: norms for object manipulability and for pictorial ambiguity of objects, chimeric objects, and nonobjects.

In this paper, we propose a standardized set of 480 black-and-white line drawings, half meaningful and half meaningless. Meaningful pictures represent a common object, and were selected from the Snodgrass and Vanderwart set (1980). Meaningless pictures include 120 chimeric objects (made up of two halves of real objects) and 120 nonobjects, that were constructed from the meaningful pictures while controlling for visual complexity. We report the results of two experiments designed to standardize the revisited Snodgrass and Vanderwart set along two important dimensions for picture processing: object manipulability (Experiment 1) and pictorial ambiguity (Experiment 2). The relevance of these dimensions is discussed. Experiment 1 permit us to sort objects into four manipulability categories (i.e., the ease and distinctiveness with which use of the object can be mimed) and to propose a manipulability index. This experiment provides additional evidence for a partial overlap in the dichotomy between man-made objects and living things, on the one hand, and manipulable and unmanipulable objects, on the other hand. In Experiment 2, a pictorial ambiguity index was computed for meaningful and meaningless pictures. The results of this experiment point the distinction between chimeric objects and nonobjects showing that chimeric objects are more complex to process than nonobjects and objects. This standardized set of pictures provides a database and an hopefully useful tool for research in cognitive neuroscience.

Nonmotor fluctuations in Parkinson's disease: frequent and disabling.

OBJECTIVE: To assess the frequency and disability caused by nonmotor fluctuations (NMF) in PD. METHODS: A structured questionnaire was administered to 50 patients with PD with motor fluctuations (MF), focused on 54 nonmotor symptoms classified in three subgroups: 26 dysautonomic, 21 cognitive and psychiatric, and seven pain/sensory NMF. The link between each NMF and the motor state was determined. Patients were asked to grade their disability from 0 (no disability) to 4 (maximum discomfort) and to specify which kind of fluctuation subgroup (motor or nonmotor) was the most incapacitating. A statistical analysis was performed to determine the frequency of each NMF and to determine whether the level of disability resulting from NMF could be correlated to the main characteristics of the population. RESULTS: All patients had had at least one type of NMF, most of which were associated with the "off" state. Anxiety (66%), drenching sweats (64%), slowness of thinking (58%), fatigue (56%), and akathisia (54%) were the most frequent NMF. Some symptoms such as anxiety or dyspnea correlated with a greater level of disability. The total number of NMF was found to be correlated with the motor disability. Incapacity resulting from the dysautonomic fluctuations was also significantly correlated with levodopa treatment. Surprisingly, 28% of the patients stated that NMF involved a greater degree of disability than MF. CONCLUSION: Nonmotor fluctuations are frequent and debilitating in PD.